title: Extracorporeal cell therapy of septic shock patients with donor granulocytes: a pilot study.
abstract: BACKGROUND
  Neutrophil granulocytes are the first defense line in bacterial infections. However, granulocytes are also responsible for severe local tissue impairment. In order to use donor granulocytes, but at the same time to avoid local side effects, we developed an extracorporeal immune support system. This first-in-man study investigated whether an extracorporeal plasma treatment with a granulocyte bioreactor is tolerable in patients with septic shock. A further intention was to find suitable efficacy end-points for subsequent controlled trials.
  
  
  METHODS
  The trial was conducted as a prospective uncontrolled clinical phase I/II study with 28-day follow-up at three university hospital intensive care units. Ten consecutive patients (five men, five women, mean age 60.3 ± 13.9 standard deviation (SD) years) with septic shock with mean ICU entrance scores of Acute Physiology and Chronic Health Evaluation (APACHE) II of 29.9 ± 7.2 and of Simplified Acute Physiology Score (SAPS) II of 66.2 ± 19.5 were treated twice within 72 hours for a mean of 342 ± 64 minutes/treatment with an extracorporeal bioreactor containing 1.41 ± 0.43 × 10E10 granulocytes from healthy donors. On average, 9.8 ± 2.3 liters separated plasma were treated by the therapeutic donor cells. Patients were followed up for 28 days.
  
  
  RESULTS
  Tolerance and technical safety during treatment, single organ functions pre/post treatment, and hospital survival were monitored. The extracorporeal treatments were well tolerated. During the treatments, the bacterial endotoxin concentration showed significant reduction. Furthermore, noradrenaline dosage could be significantly reduced while mean arterial pressure was stable. Also, C-reactive protein, procalcitonin, and human leukocyte antigen DR (HLA-DR) showed significant improvement. Four patients died in the hospital on days 6, 9, 18 and 40. Six patients could be discharged.
  
  
  CONCLUSIONS
  The extracorporeal treatment with donor granulocytes appeared to be well tolerated and showed promising efficacy results, encouraging further studies.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT00818597.
authors.affiliation: Department of Medicine, Division of Nephrology, Medical Faculty of University of Rostock, Ernst-Heydemann-Str. 6, Rostock, D-18057, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Altrichter
authors.forename: Martin
authors.initials: M
authors.lastname: Sauer
authors.forename: Katharina
authors.initials: K
authors.lastname: Kaftan
authors.forename: Thomas
authors.initials: T
authors.lastname: Birken
authors.forename: Doris
authors.initials: D
authors.lastname: Gloger
authors.forename: Martin
authors.initials: M
authors.lastname: Gloger
authors.forename: Jörg
authors.initials: J
authors.lastname: Henschel
authors.forename: Heiko
authors.initials: H
authors.lastname: Hickstein
authors.forename: Ernst
authors.initials: E
authors.lastname: Klar
authors.forename: Sebastian
authors.initials: S
authors.lastname: Koball
authors.forename: Annette
authors.initials: A
authors.lastname: Pertschy
authors.forename: Gabriele
authors.initials: G
authors.lastname: Nöldge-Schomburg
authors.forename: Dierk A
authors.initials: DA
authors.lastname: Vagts
authors.forename: Steffen R
authors.initials: SR
authors.lastname: Mitzner
mesh_terms: D000368:Aged; D003422:Critical Care / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006098:Granulocytes / Q000637:transplantation*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012772:Shock, Septic / Q000628:therapy*; D016896:Treatment Outcome